Molecular conjugates: a targeted gene delivery vector for molecular medicine.

Abstract

The use of gene therapy to treat diseases of both genetic and infectious origins has increased rapidly over the past 5 years. Accordingly, the number of delivery systems, based on either recombinant viruses or nonviral vectors, has also increased. As a result most research in this field continues to be in the area of vector development. Crucial to this aspect is the development of efficient, multipurpose therapeutic gene delivery systems which should have, but not be limited to, the following characteristics: (a) the ability to target specific cells, (b) no limitation on the size or the type of nucleic acid that can be delivered, (c) no intact viral component and therefore safe for the recipient, (d) the ability to transduce a large number of cells regardless of the mitotic status; and (e) the potential to be completely synthetic. As a step toward the development of this type of delivery system, molecular conjugates have been created. Molecular conjugates are ligands to which a nucleic acid or DNA-binding agent has been attached for the specific targeting of nucleic acids (i.e., plasmid DNA) to cells. The resulting protein/DNA complex can consist of at least four components: (a) a ligand for cell-specific targeting and receptor-mediated endocytosis, (b) a nucleic acid or DNA-binding agent (than is chemically attached to the ligand) for the binding of the DNA by ionic or other nondamaging interactions, (c) a nucleic acid, i.e., a plasmid for gene expression, and (d) an endosomal lysis agent to enhance the re-